AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Objective To investigate the etiological characteristics of food poisoning isolates of Vibrio parahaemolyticus (VP) from 2019 to 2021 in Zhongshan City. Methods A total of 37 strains of Vibrio parahaemolyticus isolated from 8 food poisoning incidents in Zhongshan City from 2019 to 2021 were collected, including 1 residual food isolate and 36 human isolates. The genetic correlation of Vibrio parahaemolyticus food poisoning isolates in this region was analyzed by serological typing, virulence gene detection (TLH, TDH, and TRH), drug sensitivity test, pulsed field gel electrophoresis (PFGE) and multipoint sequence typing (MLST). Results The 37 strains of Vibrio parahaemolyticus were divided into 4 serotypes: O3:K6, O10:K4, O4:K8, and O4:KUT. The tdh+ and trh- were the main virulence genotypes, accounting for 97.30% (36/37). The drug resistance rate of cefazolin was 40.54% (15 strains R, 22 strains I), and no multidrug-resistant strains were found. The 37 VP strains were divided into 23 PFGE types and 6 cluster groups, with correlation coefficients ranging from 60.4%-100%. The multipoint sequencing typing showed that the 37 VP strains were divided into 9 ST types and 3 complex groups, of which ST3 type was the main type (23 strains, 62.1%). Conclusion This study has found that the dominant virulence types of Vibrio parahaemolyticus food poisoning isolates in Zhongshan City from 2019 to 2021 are tdh⁺ and trh^-, and 37 representative strains can be divided into 6 PFGE clusters and 9 ST types with MLST type being mainly ST3. This study has identified the rare serotype O10:K4 which has caused an increase in the proportion of food poisoning events, suggesting that we should strengthen detection and be alert to the risk of continued local epidemics of new rare serotype strains.

Objective:To study the correction factor of the chamber wall of the reference air kerma rate reference ionization chamber (NIM-Ir-SG-100 type) for 192Ir radioactive source. Methods:The photon spectrum and ionization chamber wall correction factor of the radioactive source housing and irradiator model are calculated by Monte Carlo code. And then the photon energy, wall thickness and ionization chamber diameter, which affect the result of the chamber wall correction factor, are simulated.Results:After calculation, the simulation result of the correction factor of spherical graphite cavity ionization chamber wall was 1.037 7. Controlling a single variable, photon energy (0.3-1.3 MeV), wall thickness (0.2-0.5 cm), inner diameter (0.5 -15 cm), the maximum deviations of wall correction result were 1.62%, 3.30% and 2.86%, respectively.Conclusions:The self-made spherical graphite cavity ionization chamber has good performance, and the corrected kwall value of the chamber wall is within a reasonable range. The completion of the chamber wall correction factor is an important step to measure the reference air kerma rate of the 192Ir radioactive source and establish the measurement benchmark.

Objective:To investigate the effects of osteocalcin (BGP) on bone growth and development and the expression levels of related hormones in offspring rats under the intervention of sodium fluoride.Methods:Twenty-four clean female SD rats and 24 clean male SD rats were selected, weighing 180-220 g, and the rats were mated in a 1∶1 cage for 10 d. The fluorosis rat model was established by drinking the fluorosis water method, female rats were divided into 3 groups according to body weight by random number table method, each group of 8 rats, including the high-dose, low-dose and control groups, with sodium fluoride of 200, 100, 0 mg/L in drinking water. The female rats were exposed to fluoride from the 0th day of pregnancy to the 3rd week after the offspring rats were born (before weaning). After weaning, 10 male offspring rats were selected from each group and continued to be exposed to fluoride in the same amount and manner until the 12th week after birth. The body weight and length of the offspring rats were measured every week before weaning and every two weeks after weaning. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum BGP, parathyroid hormone (PTH), calcitonin (CT), and alkaline phosphatase (ALP) contents in the offspring rats of each group exposed to fluoride for 12 weeks.Results:In the 2nd week of fluoride exposure, the body weights [(27.25 ± 3.57), (26.27 ± 4.48) g] and body lengths [(6.92 ± 0.46), (6.50 ± 0.54) cm] of the low-dose and high-dose groups were lower than those of the control group [(31.32 ± 3.62) g, (7.19 ± 0.26) cm, P < 0.05], but there were no significant differences in body weights and lengths between the high-dose group and the low-dose group ( P > 0.05). From the 3rd week of fluoride exposure, the body weight and length of the high-dose group were lower than those of the low-dose group and the control group ( P < 0.05). Serum BGP, PTH and ALP contents [(5.42 ± 0.26) mg/L, (157.53 ± 32.21) ng/L, (36.62 ± 6.01) U/L] in the control group were lower than those of the low-dose group [(6.15 ± 0.29) mg/L, (212.26 ± 51.97) ng/L, (50.68 ± 6.11) U/L] and high-dose group [(7.31 ± 0.77) mg/L, (274.21 ± 60.32) ng/L, (74.99 ± 9.08) U/L], and CT content [(182.40 ± 17.39) ng/L] was higher than those of the low-dose and high-dose groups [(135.77 ± 14.06), (70.09 ± 13.49) ng/L], and the differences were statistically significant ( P < 0.05); serum BGP, PTH and ALP contents in the high-dose group were higher than those in the low-dose group, and the CT content was lower than that in the low-dose group ( P < 0.05). Conclusion:Sodium fluoride may be involved in regulating the expression of related hormones by promoting the secretion of BGP, thereby affecting the bone growth and development of offspring rats.

This study investigated the early mechanical adaptability and osteogenic differentiation of mouse bone marrow mesenchymal stem cells (M-BMSCs) under micro-vibration stimulation (MVS). M-BMSCs were stimulated by MVS , cell proliferation, alkaline phosphatase (ALP) activity assay, and cytoskeleton were measured, and cell apoptosis was observed by flow cytometry. Early osteoblast-associated genes, runt-related transcription factor 2 (Runx2), Collagen Ⅰ (Col-Ⅰ) and ALP, were observed by RT-PCR and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) was determined by Western blotting. The results showed that MVS had no significant effect on the proliferation of M-BMSCs. The early apoptosis was induced by mechanical stimulation (for one day), but the apoptosis was decreased after cyclic stimulation for 3 days. At the same time, MVS significantly accelerated the expression of F-actin protein in cytoskeleton, the synthesis of ALP and the ERK1/2 pathway, also up-regulated the expressions of Runx2, Col-Ⅰ and ALP genes. This study indicates that MVS could regulate cellular activity, alter early adaptive structure and finally promote the early osteogenic differentiation of M-BMSCs.

Colorectal surgery is a major therapeutic approach for various colorectal diseases. Surgery and perioperative management, such as fasting, mechanical bowel preparation, and antibiotics use, have an impact on the composition and function of gut microbiome. Abnormal microbiome reconstruction may lead to multiple complications, including infection, gastrointestinal dysfunction, anastomotic leak and disease recurrence. The aim of this review is to elucidate the roles and mechanisms of perioperative interventions of colorectal surgery on gut microbiome, which may provide a novel insight into the microbe-based therapies in the perioperative period of colorectal surgery.

Colorectal surgery is a major therapeutic approach for various colorectal diseases. Surgery and perioperative management, such as fasting, mechanical bowel preparation, and antibiotics use, have an impact on the composition and function of gut microbiome. Abnormal microbiome reconstruction may lead to multiple complications, including infection, gastrointestinal dysfunction, anastomotic leak and disease recurrence. The aim of this review is to elucidate the roles and mechanisms of perioperative interventions of colorectal surgery on gut microbiome, which may provide a novel insight into the microbe-based therapies in the perioperative period of colorectal surgery.

Objective To investigate the laparoscopic feature and its relationship with clinical manifesta-tions in infertile patients with endometriosis. Methods From Jan.2013 to Jan.2017,infertile patients who received hysteroscopy and hysteroscopy combination surgery in Ganzhou People′s Hospital were enrolled in this ret-rospective study.The basic clinical data and the distribution of endometriotic lesions were recorded and analyzed in patients with endometriosis simultaneously. Analysis was performed about the clinical manifestations and the rAFS stage of the patients. Results 204 patients are totally enrolled in the study. Among them,120 patients(58.8%) had endometriosis. The presence of menorrhea,dyspareunia,tenesmus,chronic pelvic pain,hypermenorrhea, adnexal mass,restricted uterine mobility,tenderness of adnexa,and tenderness nodules of posterior vaginal fornix are clinically statistically significant.In addition,the presence of ovarian endometrioma is also a significant clinical factor that is close related with the rAFS stage of infertile patients with endometriosis. Moreover,uterosacral liga-ment,rectovaginal septum,vagina and bowel were more common infiltrated in stage Ⅲ and stage Ⅳ endometrio-sis. Conclusions For infertile patients,detailed case history,overall bimanual examination and trans-vaginal ultrasound examination are very important to help diagnosis endometriosis preoperatively and provide evidence for the selection of individualized treatment strategies.

Objective To investigate the association between cumulative exposure blood to pressure (cum BP) and new-onset chronic kidney disease (CKD).Methods In this prospective cohort study,101 510 employees of Kailuan Group receiving annual health examination during 2006 to 2007 were observed.The participants received the second,third,and fourth annual health examinations during 2008 to 2009,2010 to 2011,and 2012 to 2013 year respectively.Their urinary and serum creatinine were tested,and participants with incomplete SBP,DBP data and CKD were excluded.Further excluding those who somehow failed to take annual health examination,with incomplete data,or new-onset CKD 27 809 participants were selected in the analysis.According to cum BP exposure quintile grouping:Q1 ＜ 3.70 scores;Q2:3.70-6.16 scores;Q3:6.17-8.45 scores;Q4:8.46-10.95scores;Q5 ≥ 10.96 scores.Multivariate Logistic regression was used to analyze the association between cum BP level and new-onset CKD by cum BP exposure quintile grouping.Results The rise of cum BP exposure level caused the increased incidence of CKD.The incidences of CKD in the five quintile groups were 2.59％,3.11％,4.19％,5.81％,and 7.73％ respectively (P＜ 0.01).Compared with Q1 group,multivariate logistic regression analysis showed that after the adjustment of age,gender,education,income,smoking,drinking,BMI,FBG,TC,TG,LDL,HDL,UA and CRP,the incidences of CKD gradually increased in the Q2,Q3,Q4,and Q5 cum BP quintile groups,and OR(95％CI) values were 1.08(0.86-1.35),1.26(1.01-1.58),1.57(1.27-1.95),1.78(1.43-2.21) respectively (P for trend ＜0.01).Similar results were obtained in different genders.For each single point increase of cum BP exposure level,the incidence of CKD increased 6％ in the general population (P for trend ＜ 0.01),increased 8％ in male (P for trend ＜ 0.01),and 3％ in female (P for trend=0.12).Conclusion As the cumulative exposure to blood pressure increases,the risk of CKD incidence rises,especially in men.